大鼠慢性鼻-鼻窦炎模型的建立及其生物学特性观察

Development of a rat model of chronic rhinosinusitis and observation of biological characteristics

目的建立大鼠慢性鼻-鼻窦炎模型的成熟方法,观察模型建立过程中各阶段炎症发生、发展的规律和特点。方法 SD大鼠60只随机分成实验组(A、B、C、D组)和对照组(E),实验组分别将膨胀海绵片置入大鼠左侧鼻腔,距离前鼻孔约15 mm,位于窦口鼻道复合体处,金黄色葡萄球菌标准菌株悬浊液左侧鼻腔内灌注。于术前及术后3 d、4周、8周、12周行内眦静脉/腹主动脉取血查血常规。实验组分别于术后3 d、4周、8周、12周处死,解剖并取双侧上颌窦黏膜行病理切片及双侧鼻腔分泌物培养。对照组直接处死,取双侧上颌窦黏膜行病理切片及双侧鼻腔分泌物培养。结果大鼠慢性鼻-鼻窦炎造模过程中,实验组术后3 d、4周、8周血常规白细胞计数值均显著高于术前和对照组(P<0.01),并在4周之内保持高水平。术后1 2周时血常规白细胞计数值较术前和对照组无明显差异(P>0.0 5)。实验组大鼠9 5.7%(44/46)发生鼻中隔穿孔,多位于鼻中隔前下部,术后3 d内即可发生。解剖发现3 d以上各实验组双侧鼻窦均有大量脓性分泌物,术后8～12周各鼻窦脓性分泌物明显减少。病理切片显示,术后第4～12周,实验组左侧上颌窦黏膜炎症由亚急性向慢性迁延。C、D组右侧上颌窦黏膜8、12周同左侧上颌窦黏膜有相似程度的炎症。分泌物培养显示,术后第4周36.4%双侧鼻腔均培养出金黄色葡萄球菌,其他培养结果均为条件致病菌。术后12周所有培养均未检出金黄色葡萄球菌。66.7%的双侧鼻腔培养为条件致病菌,其余未检出细菌。结论鼻腔膨胀海绵填塞可有效建立大鼠慢性鼻-鼻窦炎模型,术后约4周的急性期,逐渐转向慢性炎症,至12周形成稳定的慢性炎症。此时是进行进一步干预研究的成熟时机。细菌感染与慢性鼻-鼻窦炎的炎症持续状态并无明确相关性。

Objective To develop a rat model of rhinogenic chronic rhinosinusitis biological characteristics during succession of inflammation. Methods Animals （n = unilateral maxillary sinus ostial obstruction using Merocel nasal packing with standard inoculation were examined for blood routine examination before operation and at 3 days, 4, （ CRS ） and observe 4 8 ） that underwent staphylococcus aureus 8 and 1 2 weeks after operation. Following sacrifice at 3 days, 4, 8 and 1 2 weeks, the obtained maxillary sinuses were prepared for histologic investigation and bacterial culture. Experimental interventions were compared with normal controls （ n = 12 ） and with contralateral control sinuses within each animal. Results White blood cell counts （WBC） at 3 days, 4,and 8 weeks were significant higher than that of controls （ P 〈 0. 01 ） , and the peak was in 4 weeks , while WBC at 12 weeks descended to the normal （ P 〉 0. 05 ） . Perforation of nasal septum , was observed in 95. 7 % of the animals （44/46） , within 3 days, which almost located in anteroinferior of the nasal septum. Anatomical and histologic characteristics of chronic sinonasal inflammation were gradually present and stable from 4 to 12 weeks. The similar inflammation happened in the contralateral control sinuses within each animal as compared with the experimental sinuses. Standard staphylococcus aureus was detected in 36. 4 % of bilateral sinuses at 4 weeks, while none at 12 weeks but conditional pathogenic bacterium in 66.7 % of bilateral sinuses. Conclusion Unilateral maxillary sinus ostial obstruction using Merocel nasal packing with standard staphylococcus aureus inoculation results in a persistent, stable CRS in rat until 12 weeks after operation, when further investigations into disease pathophysiology would be appropriate. No more evidence demonstrates that infection contributes to the persistence and stability of inflammation of CRS.